Association of Antibody to GB Virus C (Hepatitis G Virus) with Viral Clearance and Protection from Reinfection

Abstract

GB virus C (GBV-C) RNA and envelope antibody were assessed in a median of 4 samples collected over 6.5 years among injection drug users (IDUs). A marker of GBV-C infection was detected in 110 (94.8%) of 116 IDUs. GBV-C RNA was detected at all visits in 32, was never detected in 70, was acquired in 7, and was cleared in 8. The odds of detecting anti-GBV-C were 103-fold higher in participants without detectable RNA (64 of 70) than in IDUs with persistent RNA (3 of 32; P < 10(-7)). Anti-GBV-C was detected in all 8 instances of RNA clearance. GBV-C RNA never reappeared once it was cleared, and there were no new GBV-C infections among 61 anti-GBV-C-positive IDUs observed for 382 person-years, though all had ongoing drug use. Studies using RNA testing alone may significantly underestimate the occurrence of GBV-C infection. Anti-GBV-C is highly associated with viral clearance and protection from reinfection.

Full-Length GB Virus C (Hepatitis G Virus) RNA Transcripts Are Infectious in Primary CD4-Positive T Cells

“…In addition, GBV-C and HCV appear to utilize the lowdensity lipoprotein receptor for viral entry (1). Thus, comparison of GBV-C and HCV may provide insight into the reasons why HCV does not appear to replicate as efficiently in cell culture as GBV-C and why GBV-C is cleared more efficiently by the host immune response than HCV (17,47,48). Although several infectious HCV clones have been described, all of these rely on inoculation of transcribed RNA into susceptible primate species, and none were shown to be infectious in vitro (7,18,22,53,54).…”

“…Nonetheless, persistent GBV-C viremia (as detected by reverse transcriptase PCR [RT-PCR]) is common, with 0.9 to 3% of healthy U.S. blood donors and approximately 20 to 30% of patients with HCV infection persistently infected with GBV-C (11,15,17,41,42,45). Following infection, about 80% of people clear their viremia, concomitantly developing antibodies to the GBV-C E2 protein (15,17,47). Thus, it is estimated that approximately 20% of infected people remain viremic for long periods of time.…”

An 85-aa segment of the GB virus type C NS5A phosphoprotein inhibits HIV-1 replication in CD4 + Jurkat T cells

“…Because of shared modes of transmission, up to 86% of HIVpositive individuals have evidence of active (39.6%) or prior (46%) GBV-C infection (1,2). Although viremia may persist for decades in some individuals, most immune-competent hosts clear GBV-C infection concurrently with the development of antibodies to the envelope glycoprotein E2 (3,4), which appear to confer some, although not complete, protection against reinfection (4). Although no disease entity has yet been associated with GBV-C infection (reviewed in refs.…”

Characterization of an Immunodominant Antigenic Site on GB Virus C Glycoprotein E2 That Is Involved in Cell Binding

“…However, immunocompetent people infected with GBV-C who clear viremia develop E2 antibodies (3,34) and these antibodies appear to be partly protective against reinfection following liver transplantation, suggesting neutralizing activity (9,35). Only group I GBV-C E2 MAbs inhibited PcAb independently, and none of the MAbs tested demonstrated more than 50% inhibition when competing with human polyclonal E2 antibody individually.…”

“…Although persistent infection occurs in some individuals, the majority of infected people who are immune competent clear GBV-C within 2 years following acquisition (24,30,31,32). Clearance is associated with the development of E2 antibodies (3,30,31,32,34), which appear to provide some protection against reinfection (9, 35), suggesting that these antibodies are neutralizing.…”